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In Fallout 3, Mirelurks are found in three variants: Mirelurks, mutated forms of Chesapeake Bay Blue Crabs (Callinectes sapidus); mirelurk hunters, mutated Atlantic Horseshoe Crabs (Limulus polyphemus); and in the form of Mirelurk kings, mutated snapping turtles. They can deal massive damage, and can absorb a great deal in return thanks to their shells. Generally, they can be found near sources of water, including the Potomac River in groups of two or more individuals of one of the above groupings.

In Fallout New Vegas, a strain of mutated turtles native to Lake Mead and other large water bodies appears; resembling the Mirelurk Kings of the Capital Wasteland, these humanoid turtles are called lakelurks by the locals.

In Fallout 4, mirelurks appear markedly more crab-like in appearance than those in Fallout 3, and their posture is generally crouched down to make their vulnerable faces harder to hit. Their shells also possess a mild reflective quality, as lasers ricochet off them. Mirelurk hunters appear to be mutant lobsters or crayfish rather than crabs. Mirelurk kings are less bipedal, have more prominent fins and have a long tail. Fallout 4 also adds the mirelurk queen, a gigantic creature slightly taller than a super mutant behemoth.

Considerably larger and more dangerous than the other mirelurks. They have very large health pools, to the point they can even take several mini nukes to the torso without dying. One spawns at the Castle in Fallout 4 during the quest Taking Independence.